We request funding to support the next three Federation of American Society of Experimental Biologists (FASEB) Summer Conferences on "Protein Folding in the Cell," beginning with the 2002 meeting to be held July 27 to August 1, in Saxtons River, VT. The proposed conferences will be the seventh, eighth, and ninth in a series of highly successful FASEB Conferences on this topic. This meeting is unique in its goal of bringing together cell biologists/geneticists and biophysicists/biochemists to tackle the complex problems of protein folding and misfolding and implications for human disease. This was the concept behind the first conference in 1990, and it remains a unique opportunity for scientists from very diverse backgrounds. Most protein folding conferences consider either the theoretical and in vitro aspects of folding or the role of molecular chaperones and protein folding catalysts in the cell. However, the need for interdisciplinary approaches is stronger than ever. The cell biology has progressed to where reaching a mechanistic understanding is crucial, and biological constraints play a critical role in formulating theory and interpreting in vitro data. In addition to examining recent advances in in vitro folding and molecular chaperone mechanism, this meeting will focus on protein translocation across membranes, protein misfolding in diseases, folding of membrane proteins, folding of metalloproteins, newly recognized roles of chaperones in signal transduction, and protein degradation. Misfolding of proteins and potential consequences are of central importance in human disease. Finding therapeutic strategies requires a fundamental understanding of the behavior of the polypeptide chain and the cellular environment and constraints imposed on it. Our goal is to bring together physical and biological scientists in an interactive environment, to promote education and understanding of the approaches, experimental limitations and to explore common interests. The small size and isolated setting of this meeting with all participants residing and taking their meals in close proximity promotes optimal scientific exchange. The conference format will provide extensive arenas for informal discussions. Poster sessions will allow all participants to interact scientifically with other investigators. Young investigators and women will be well-represented among speakers and encouraged to attend the conference.